TCRs directed against tumor-associated antigens (TAA) can result in serious off-tumor on-target toxicity, for example uveitis, labyrinthitis, vitiligo, and death of melanoma patients upon targeting the melanocytic differentiation antigens MART-1 and gp100, due to cross-reaction with normal melanocytes and cytokine release [29,30]. This evidence concerns the gene PMEL and neoplasm.